Expression of Fibrosis-Related Genes in Canine Chronic Hepatitis
VETERINARY PATHOLOGY
Authors: Kanemoto, H.; Ohno, K.; Sakai, M.; Nakashima, K.; Takahashi, M.; Fujino, Y.; Tsujimoto, H.
Abstract
Molecular regulation of fibrosis in chronic canine hepatitis is poorly understood. The authors employed quantitative polymerase chain reaction (PCR) to determine the expression levels of genes reported to be related to fibrosis in other species (human, mouse, and rat) and to elucidate the relationship of these genes with the degree of fibrosis and the presence or absence of ascites and/or jaundice in dogs with hepatitis. Nine fibrosis-related genes were assayed: PDGFB, PDGFD, MMP2, TIMP1, THBS1, COL1A1, COL3A1, TGFB1, and TGFB2. Liver samples of 15 dogs with chronic hepatitis and 4 healthy control dogs were obtained via laparoscopic biopsy and subjected to histologic and quantitative PCR analyses. The expression of all 9 genes showed significant positive correlation (P < .01, r > .70) with the degree of fibrosis. Furthermore, the expression levels of all genes except TGFB1 were significantly higher (P < .05) in dogs with hepatic failure-related symptoms (ascites/jaundice). Results suggest that these 9 genes are integral to the development of fibrosis in canine chronic hepatitis.
The autophagy protein Ambra1 regulates gene expression by supporting novel transcriptional complexes
JOURNAL OF BIOLOGICAL CHEMISTRY
Authors: Schoenherr, Christina; Byron, Adam; Griffith, Billie; Loftus, Alexander; Wills, Jimi C.; Munro, Alison F.; von Kriegsheim, Alex; Frame, Margaret C.
Abstract
Ambra1 is considered an autophagy and trafficking protein with roles in neurogenesis and cancer cell invasion. Here, we report that Ambra1 also localizes to the nucleus of cancer cells, where it has a novel nuclear scaffolding function that controls gene expression. Using biochemical fractionation and proteomics, we found that Ambra1 binds to multiple classes of proteins in the nucleus, including nuclear pore proteins, adaptor proteins such as FAK and Akap8, chromatin-modifying proteins, and transcriptional regulators like Brg1 and Atf2. We identified biologically important genes, such asAngpt1,Tgfb2,Tgfb3,Itga8, andItgb7, whose transcription is regulated by Ambra1-scaffolded complexes, likely by altering histone modifications and Atf2 activity. Therefore, in addition to its recognized roles in autophagy and trafficking, Ambra1 scaffolds protein complexes at chromatin, regulating transcriptional signaling in the nucleus. This novel function for Ambra1, and the specific genes impacted, may help to explain the wider role of Ambra1 in cancer cell biology.
COA
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